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https://www.readbyqxmd.com/read/28421460/flow-arrest-intra-arterial-delivery-of-small-tat-decorated-and-neutral-micelles-to-gliomas
#1
Juliane Nguyen, Shaolie S Hossain, Johann R N Cooke, Jason A Ellis, Michael B Deci, Charles W Emala, Jeffrey N Bruce, Irving J Bigio, Robert M Straubinger, Shailendra Joshi
The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide derived from human immunodeficiency virus-1. It has been used to facilitate macromolecule delivery to various cell types. This cationic peptide is capable of crossing the blood-brain barrier and therefore might be useful for enhancing the delivery of drugs that target brain tumors. Here we test the efficiency with which relatively small (20 nm) micelles can be delivered by an intra-arterial route specifically to gliomas. Utilizing the well-established method of flow-arrest intra-arterial injection we compared the degree of brain tumor deposition of cationic TAT-decorated micelles versus neutral micelles...
April 18, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28419874/oral-administration-of-a-specific-kynurenic-acid-synthesis-kat-ii-inhibitor-attenuates-evoked-glutamate-release-in-rat-prefrontal-cortex
#2
D M Bortz, H-Q Wu, R Schwarcz, J P Bruno
Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict patient outcome; however, they remain poorly treated by current antipsychotic drugs. Elevated levels of the endogenous alpha7 nicotinic receptor negative allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ. When acutely or chronically elevated in rodents, KYNA produces cognitive deficits similar to those seen in the disease, making down-regulation of KYNA, via inhibition of kynurenine aminotransferase II (KAT II), a potential treatment strategy...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28391443/non-human-primate-models-of-pd-to-test-novel-therapies
#3
REVIEW
Marc Morissette, Thérèse Di Paolo
Non-human primate (NHP) models of Parkinson disease show many similarities with the human disease. They are very useful to test novel pharmacotherapies as reviewed here. The various NHP models of this disease are described with their characteristics including the macaque, the marmoset, and the squirrel monkey models. Lesion-induced and genetic models are described. There is no drug to slow, delay, stop, or cure Parkinson disease; available treatments are symptomatic. The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-Dopa) still remains the gold standard symptomatic treatment of Parkinson...
April 8, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28362421/a-protocol-for-rapid-post-mortem-cell-culture-of-diffuse-intrinsic-pontine-glioma-dipg
#4
Grant L Lin, Michelle Monje
Diffuse Intrinsic Pontine Glioma (DIPG) is a childhood brainstem tumor that carries a universally fatal prognosis. Because surgical resection is not a viable treatment strategy and biopsy is not routinely performed, the availability of patient samples for research is limited. Consequently, efforts to study this disease have been challenged by a paucity of faithful disease models. To address this need, we describe here a protocol for the rapid processing of post-mortem autopsy tissue samples in order to generate durable patient-derived cell culture models that can be used in in vitro assays or in vivo orthotopic xenograft experiments...
March 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28349246/suicide-patterns-in-children-and-adolescents-a-review-from-a-pediatric-institution-in-england
#5
Khairul Zainum, Marta C Cohen
Suicide is a catastrophic event to both families and communities yet it is potentially preventable. This study aims to determine incidence and patterns of suicide in children and young adolescents in our region, raise awareness of this entity as a potentially preventable cause of death in this age group, and identify its possible associated risk factors. We retrospectively reviewed suicide cases presenting as sudden unexpected death in children and adolescents that underwent coronial post-mortems at our institution...
March 27, 2017: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/28345587/derivation-of-functional-human-astrocytes-from-cerebral-organoids
#6
Rômulo Sperduto Dezonne, Rafaela Costa Sartore, Juliana Minardi Nascimento, Verônica M Saia-Cereda, Luciana Ferreira Romão, Soniza Vieira Alves-Leon, Jorge Marcondes de Souza, Daniel Martins-de-Souza, Stevens Kastrup Rehen, Flávia Carvalho Alcantara Gomes
Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28340719/application-of-a-rapid-%C3%AE-spe-clean-up-for-multiclass-quantitative-analysis-of-sixteen-new-psychoactive-substances-in-whole-blood-by-lc-ms-ms
#7
Camilla Montesano, Gabriele Vannutelli, Valeria Piccirilli, Manuel Sergi, Dario Compagnone, Roberta Curini
Europe is an important market for illegal drugs, and nowadays a lot of new different psychoactive substances (NPS) are widespread. This work reports the development of a method to determine simultaneously different classes of NPS, as synthetic cannabinoids (SC) and their metabolites, cathinones and phenetylamines, directly on whole blood (WB) without anti-coagulants and using miniaturized solid phase extraction (μ-SPE). In order to demonstrate the feasibility of the method 16 different NPS belonging to the mentioned classes were selected for the analysis...
May 15, 2017: Talanta
https://www.readbyqxmd.com/read/28339816/post-mortem-toxicology-in-young-sudden-cardiac-death-victims-a-nationwide-cohort-study
#8
Thea Bjune, Bjarke Risgaard, Line Kruckow, Charlotte Glinge, Ole Ingemann-Hansen, Peter Mygind Leth, Kristian Linnet, Jytte Banner, Bo Gregers Winkel, Jacob Tfelt-Hansen
Aims: Several drugs increase the risk of ventricular fibrillation and sudden cardiac death (SCD). We aimed to investigate in detail the toxicological findings of all young SCD throughout Denmark. Methods and results: Deaths in persons aged 1-49 years were included over a 10-year period. Death certificates and autopsy reports were retrieved and read to identify cases of sudden death and establish cause of death. All medico-legal autopsied SCD were included and toxicological reports collected...
February 27, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28335036/validated-method-for-the-screening-and-quantification-of-baclofen-gabapentin-and-pregabalin-in-human-post-mortem-whole-blood-using-protein-precipitation-and-liquid-chromatography-tandem-mass-spectrometry
#9
Limon Nahar, Amy Smith, Rajan Patel, Rebecca Andrews, Sue Paterson
There has been a rapid increase in the number of prescriptions for baclofen (BLF), gabapentin (GBP) and pregabalin (PGL) in the UK since their introduction to therapy. Recent studies across the European Union and USA have shown the illicit abuse potential of these drugs and deaths have been observed. A simple, reliable and fully validated method was developed for the screening and quantification of BLF, GBP and PGL in human post-mortem (PM) blood. The analytes and their deuterated analogs as internal standard were extracted from blood using a single addition acetonitrile protein precipitation reaction followed by analysis using liquid chromatography-tandem mass spectrometry (LC-MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous confirmation and quantification...
March 10, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28276094/pathology-of-toxic-leucoencephalopathy-in-drug-abuse-supports-hypoxic-ischemic-pathophysiology-etiology
#10
Murad Alturkustani, Lee-Cyn Ang, David Ramsay
The histopathological features of leucoencephalopathy caused by illicit drugs (such as opioids and cocaine) are well documented in acute cases but not in long-survival cases. There are several hypotheses about the pathogenesis of this disorder, including hypoperfusion, direct drug toxicity resulting from the neurotoxic effects of the drug itself or contaminants in the illicit drug vehicle. We reviewed the post mortem findings in five males (aged 24 to 56 years, with survival intervals ranging from 7 days to 5 months) with a history of illicit drug use and concomitant fatal white matter changes...
March 9, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28270242/to-see-or-not-to-see-non-invasive-imaging-for-improved-readout-of-drug-treatment-trials-in-the-murine-model-of-secondary-alveolar-echinococcosis
#11
D Gorgas, N Marreros, R Rufener, A Hemphill, B Lundström-Stadelmann
Alveolar echinococcosis (AE) is an emerging zoonotic disease caused by the cestode Echinococcus multilocularis. The secondary infection model of AE is based on intraperitoneal injection of disease-causing metacestodes into the peritoneal cavity of mice, which allows investigations on novel drugs or immunotherapeutical treatment options in vivo. So far, such in vivo studies assessed exclusively the parasite weight at the endpoint of a given treatment period. We here developed an ultrasound (US)-based scoring system that allows to follow-up parasite development in the living animal, and provides insights into parasite growth during the treatment phase...
March 8, 2017: Parasitology
https://www.readbyqxmd.com/read/28260886/convection-enhanced-delivery-of-panobinostat-lbh589-loaded-pluronic-nano-micelles-prolongs-survival-in-the-f98-rat-glioma-model
#12
W G Singleton, A M Collins, A S Bienemann, C L Killick-Cole, H R Haynes, D J Asby, C P Butts, M J Wyatt, N U Barua, S S Gill
BACKGROUND: The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood-brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). MATERIALS AND METHODS: The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28241065/repeated-dexamphetamine-treatment-alters-the-dopaminergic-system-and-increases-the-phmri-response-to-methylphenidate
#13
Anouk Schrantee, Jordi L Tremoleda, Marzena Wylezinska-Arridge, Valentine Bouet, Peter Hesseling, Gideon F Meerhoff, Kora M de Bruin, Jan Koeleman, Thomas Freret, Michel Boulouard, Emilie Desfosses, Laurent Galineau, Alessandro Gozzi, François Dauphin, Willy Gsell, Jan Booij, Paul J Lucassen, Liesbeth Reneman
Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA) neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart), followed by a 1-week washout period. We then used pharmacological MRI (phMRI) with a methylphenidate (MPH) challenge, as a sensitive and non-invasive in-vivo measure of DAergic function...
2017: PloS One
https://www.readbyqxmd.com/read/28192174/does-genetic-bdnf-deficiency-in-rats-interact-with-neurotransmitter-control-of-prepulse-inhibition-implications-for-schizophrenia
#14
Maarten van den Buuse, Davina Biel, Kathrin Radscheit
Several studies have suggested a role of BDNF in the development of schizophrenia. For example, post-mortem studies have shown significantly reduced levels of BDNF protein expression in the brain of schizophrenia patients. We investigated the relationship between reduced levels of BDNF in the brain and the regulation of prepulse inhibition (PPI), a behavioral endophenotype of schizophrenia. We used BDNF heterozygous mutant rats which display a 50% decrease of mature BDNF protein levels. Previously, we observed normal baseline PPI and responses to the dopamine D1/D2 receptor agonist, apomorphine, in these rats...
April 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28138041/translational-pharmacology-of-the-mglur2-preferring-agonist-ly2812223-in-animal-and-human-brain
#15
Christian C Felder, Douglas A Schober, Yuan Tu, Anne T Quets, Hongling Xiao, Marla Watt, Edward R Siuda, Eric S Nisenbaum, Chuanix Xiang, Beverly Heinz, Lourdes Prieto, David L Mc Kinzie, James A Monn
LY2812223 was identified via structure-activity studies arising from the potent mGlu2/3 receptor agonist LY354740 as a selective mGlu2 agonist. This pharmacology was determined using cells stably transfected cells either containing the human mGlu2 or mGlu3 receptor. We extended the pharmacological evaluation of LY2812223 to native brain tissues derived from relevant species used for preclinical drug development as well as human post mortem brain tissue. This analysis was conducted to ensure pharmacological translation from animals to human subjects in subsequent clinical studies...
January 30, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28135061/neurocytometry-flow-cytometric-sorting-of-specific-neuronal-populations-from-human-and-rodent-brain
#16
David Martin, Jiaxi Xu, Connie Porretta, Charles D Nichols
Flow cytometry has the potential to facilitate understanding of the heterogeneous responses of diverse brain cell populations to a variety of stimuli. However, existing methods of applying flow cytometry to brain tissues are each limited in certain ways. They either require genetically labeled cells to achieve separation of specific populations, are not applicable to previously fixed tissue, or are not compatible with downstream mRNA analysis. Here, we describe a group of related methods that overcome many previous limitations and allow robust sorting and downstream molecular analysis of highly enriched populations of specific neuronal and non-neuronal cells from any mammalian brain...
February 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28110168/ultra-high-performance-liquid-chromatography-tandem-mass-spectrometry-uhplc-ms-ms-for-determination-of-ghb-precursors-and-metabolites-in-different-specimens-application-to-clinical-and-forensic-cases
#17
Francesco Paolo Busardò, Chrystalla Kyriakou, Emilia Marchei, Roberta Pacifici, Daniel Sejer Pedersen, Simona Pichini
Gamma-hydroxybutyric acid (GHB) acts as a precursor and metabolite of the inhibitory central nervous system (CNS) neurotransmitter gamma-aminobutyric acid (GABA). Sodium salt of GHB has been used as a medication for narcolepsy and alcohol withdrawal. Moreover, GHB and its precursor gamma-butyrolactone (GBL), are illegal recreational drugs of abuse. A procedure based on ultra-high-performance liquid chromatography tandem mass spectrometry has been developed and validated in plasma, urine, cerebrospinal fluid and hair for acute and chronic exposure to GHB and in seized preparations coming from black market...
January 9, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28107458/neuropilin-1-involvement-in-choroidal-and-retinal-neovascularisation
#18
Patricia Fernández-Robredo, Senthil Selvam, Michael B Powner, Dawn A Sim, Marcus Fruttiger
PURPOSE: Inhibiting VEGF is the gold standard treatment for neovascular age-related macular degeneration (AMD). It is also effective in preventing retinal oedema and neovascularisation (NV) in diabetic retinopathy (DR) and retinal vein occlusions (RVO). Neuropilin 1 (Nrp1) is a co-receptor for VEGF and many other growth factors, and therefore a possible alternative drug target in intra ocular neovascular disease. Here we assessed choroidal and retinal NV in an inducible, endothelial specific knock out model for Nrp1...
2017: PloS One
https://www.readbyqxmd.com/read/28041969/needle-free-injection-of-vesicular-phospholipid-gels-a-novel-approach-to-overcome-an-administration-hurdle-for-semisolid-depot-systems
#19
Michaela Breitsamer, Gerhard Winter
Vesicular phospholipid gels (VPGs) are depot formulations for the sustained release of drugs which are characterized by a high amount of phospholipids in the formulation. They consist of physiological excipients only and therefore display high biocompatibility. Their manufacture is simple, cheap, solvent free, and ideal for the processing of proteins and peptides because of the low stress on the molecule, for example, by elevated temperatures. One major hurdle of VPGs is their high viscosity which makes them hard to almost impossible to inject with conventional, thin needles used for subcutaneous administration...
December 29, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28039081/neurologic-complications-after-allogeneic-hematopoietic-stem-cell-transplantation
#20
REVIEW
Enrico Maffini, Moreno Festuccia, Lucia Brunello, Mario Boccadoro, Luisa Giaccone, Benedetto Bruno
Neurologic complications after hematopoietic stem cell transplantation are frequently life-threatening, and their clinical management can be highly challenging. A wide spectrum of causative factors-including drug-related toxicities; infections sustained by virus, bacteria, or invasive molds; metabolic encephalopathy; cerebrovascular disorders; immune-mediated disorders; and disease recurrence-may lead to potentially lethal complications. Moreover, given that some neurologic complications are not uncommonly diagnosed post mortem, their overall incidence is likely to be underestimated...
December 27, 2016: Biology of Blood and Marrow Transplantation
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